Ketoaldehyde intramolecular aldol reaction

Ketoaldehyde (55) undergoes a hydroxide-catalysed intramolecular aldol reaction. Initial deprotonation gives an enolate. This step has been shown to be effectively irreversible by determination of the rate constant ratio for the two possible fates of the... 

In contrast to the early report of intramolecular desymmetrization reactions [6], the intramolecular ring-closing reactions of achiral substrates via enamine catalysis were not disclosed until the beginning of the twenty-first century. In 2003, list reported the first highly stereoselective intramolecular aldol reaction of achiral dicarbonyl compounds. Cyclic aldol products 6a-< were delivered from heptanedials 5 with excellent diastereo- and enantioselectivity by the catalysis of L-proline (Scheme 36.2). The cyclization of ketoaldehyde 7 afforded alcohol 8 as a 2 1 diastereomeric mixture but with 99% ee. This strategy could provide P hydroxyl carbonyl derivatives that are of potential applications in organic synthesis [7aj. 

Other removal procedures include reaction of the bicyclic lactam 4 with hydride (R6 = H) or an alkyl metal (R6 = alkyl). After hydrolysis of the bicyclic azahemiketal 5, ketoaldehydes or diketones 6 result. These can then be used in intramolecular aldol-type reactions to furnish enantiomerically pure cyclopentenones 7 (n = 1). The same reaction sequence can be used to prepare cyclohexenones (see Table 9)3-6 7l 1 ... 

Fukuyama also presented an alternative route to the advanced intermediate 114 as shown in Scheme 18 with an early introduction of the protected amino functionality. Reaction of y-butyrolactone with the Grignard reagent derived from 1,4-dibromobutane (120) afforded diol 121. Mesylation of the primary hydroxyl functionality with concomitant elimination of the tertiary one was followed by reaction with methylamine and protection of the resulting secondary amine to give alkene 122. Ozonolysis of the double bond in 122 and subsequent intramolecular aldol condensation of the resulting ketoaldehyde afforded cycohexenone 123. Rubottom oxidation and acetylation gave 124, which served as substrate in the lipase-... 

In an intramolecular case, it was shown that, in an aqueous medium, the nature of the acidic or basic catalyst had a dramatic effect on the outcome of the aldolisation (Denmark and Lee, 1992). Acid-induced aldol condensation of ketoaldehyde 1 provided the syn hydroxyketone 2, while the anti isomer 3 arose from base-catalyzed reactions ... 

The aqueous medium influences not only the reaction rate but also the stereoselection of the aldol addition. One significant example [13] is the intramolecular cyclization of ketoaldehyde depicted in Scheme 7.2. In organic solvents there is a preference for syn or anti adduct depending on the presence of coordinating cations (K, Na, Li, MgBr ) or a complexing agent such as... 

---